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Case-control study of genotypes in multiple chemical sensitivity: CYP2D6, NAT1, NAT2, PON1, PON2 and MTHFR

Gail McKeown-Eyssen1, Cornelia Baines, David E C Cole

  • 1Departments of Public Health Sciences, University of Toronto, ON, Canada. gail.eyssen@utoronto.ca

International Journal of Epidemiology
|July 17, 2004
PubMed
Abstract

Insights

Genetic variations in drug-metabolizing enzymes like CYP2D6 and NAT2 are linked to multiple chemical sensitivity (MCS). Rapid metabolism of certain chemicals may significantly increase MCS risk, suggesting a genetic predisposition.

Area of Science:

  • Environmental Health
  • Toxicology
  • Human Genetics

Background:

  • Multiple chemical sensitivity (MCS) is hypothesized to involve impaired metabolism of toxic chemicals.
  • Genetic variations in enzymes affect chemical metabolism rates, prompting investigation into their role in MCS.

Purpose of the Study:

  • To investigate if genetic polymorphisms in drug-metabolizing enzymes differ between individuals with MCS and healthy controls.
  • To identify specific genetic variations associated with an increased risk of developing MCS.

Main Methods:

  • A case-control study involving 203 female Caucasian MCS cases and 162 controls.
  • Genotyping was performed for common polymorphisms in CYP2D6, NAT1, NAT2, PON1, and PON2 enzymes.

Main Results:

  • Significant differences in genotype distributions were observed for CYP2D6 (P = 0.02) and NAT2 (P = 0.03) between cases and controls.
  • Higher odds of being a rapid metabolizer for CYP2D6 (OR=3.36) and NAT2 (OR=4.14) were found in MCS cases.
  • Increased odds for PON1 heterozygosity (PON1-55: OR=2.05; PON1-192: OR=1.57) were also associated with MCS.
  • A significant gene-gene interaction between CYP2D6 and NAT2 indicated substantially elevated MCS risk (OR=18.7) for rapid metabolizers of both enzymes.

Conclusions:

  • Genetic predisposition, particularly altered biotransformation of environmental chemicals via enzymes like CYP2D6 and NAT2, may play a role in MCS.
  • The findings suggest that genetically variable toxin pathways could be crucial in MCS pathogenesis.
  • Further research, including replication studies, is needed to confirm the association between genetic variations in drug-metabolizing enzymes and MCS.

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